Microscopic examination of tissue samples, particularly those obtained by biopsy, is a common method for diagnosis of disease. In particular, immunohistochemistry (IHC), a technique in which specific antibodies are used to detect expression of specific proteins in the tissue sample, is a valuable tool for diagnosis, particularly for the detection and diagnosis of cancer.
Uroplakins (UPs) comprise a group of 4 transmembrane proteins (UPs Ia, Ib, II, and III) expressed in the luminal surface of normal urothelial superficial (umbrella) cells, which are specific differentiation products of urothelial cells. Uroplakin III (UP III) is a 47 kDa glycoprotein that may be a useful marker in cancer diagnosis. Moll et. al. reported that, when using an anti-UP III rabbit polyclonal antibody, UP III may be immunohistochemically detectable in 29 of 55 (53%) and 23 of 35 (66%) primary and metastatic urothelial carcinomas, respectively; whereas, a large number of non-urothelial carcinomas were consistently UP III-negative. (See Moll R, Wu X, Lin J, Sun T; Am J Pathol. 1995; 147:1383-1397, hereby incorporated by reference herein.) The authors concluded that UP III should be a valuable immunohistochemical marker, especially for the highly specific identification of urothelial carcinomas in patients with a metastatic carcinoma of unknown primary site; however, these antibodies were not readily available from commercial sources.
A mouse monoclonal antibody to Uroplakin III was developed [clone AU 1] and offered commercially by PROGEN, Heidelberg, Germany. In a study by Kaufmann et. al. (See Kaufmannn O, Volmerig J, Dietel M; Am J Clin Pathol. 2000; 113:683-687, hereby incorporated by reference herein), AU 1 was shown to be a moderately sensitive and highly specific antibody for urothelial tumors. This study demonstrated an overall sensitivity of 57% for AU 1 staining of primary and metastatic urothelial carcinomas. Importantly, this sensitivity was determined using a cut-off value of 1% of tumor cells staining positive for AU 1 as the criteria for identifying a case as positive for AU 1. Amongst practicing pathologists, such a cut-off value of 1% for determining positivity would be unusually low criteria in these types of cases. As a result, the sensitivity of AU 1 routinely observed in clinical diagnosis (where a higher cut-off, such as between about 5 and about 10% of tumor cells staining, may be the standard practice) is much lower than that reported by Kaufmann et. al. Consequently, the conclusion amongst practicing pathologists may be that AU 1 is not sufficiently sensitive to be a useful marker in the diagnosis of urothelial carcinoma and it may not be commonly used. The sensitivity reported by Kaufmann et. al. may not have been reproduced or validated in the literature in the 12 years since its publication, as may be typical for a diagnostically useful marker. It is generally known amongst pathologists that the poor sensitivity of anti-UP III (AU 1) may prevent its use as a reliable marker for TCC and a more sensitive anti-UP III antibody is desired in the field.
A clear need exists for an anti-Uroplakin III antibody with greater sensitivity than AU 1 for use in cancer diagnosis. A new anti-Uroplakin III antibody with increased staining sensitivity, while preserving equal or superior staining specificity compared to clone AU1, has been developed. Additional information may be found in patent application No. 61/706,312 filed Sep. 27, 2012 entitled “Systems and Methods for Anti-Uroplakin II Antibodies” and PCT application no. PCT/US2012/037367 filed May 10, 2012 entitled, “Systems and Methods for Anti-PAX8 Antibodies”, each hereby incorporated by reference herein in their entirety.